Mitochondrial remodeling underlying age-induced skeletal muscle wasting: let's talk about sex.

Sarcopenia is associated with reduced quality of life and premature mortality. The sex disparities in the processes underlying sarcopenia pathogenesis, which include mitochondrial dysfunction, are ill-understood and can be decisive for the optimization of sarcopenia-related interventions. To improve the knowledge regarding the sex differences in skeletal muscle aging, the gastrocnemius muscle of young and old female and male rats was analyzed with a focus on mitochondrial remodeling through the proteome profiling of mitochondria-enriched fractions. To the best of our knowledge, this is the first study analyzing sex differences in skeletal muscle mitochondrial proteome remodeling. Data demonstrated that age induced skeletal muscle atrophy and fibrosis in both sexes. In females, however, this adverse skeletal muscle remodeling was more accentuated than in males and might be attributed to an age-related reduction of 17beta-estradiol signaling through its estrogen receptor alpha located in mitochondria. The females-specific mitochondrial remodeling encompassed increased abundance of proteins involved in fatty acid oxidation, decreased abundance of the complexes subunits, and enhanced proneness to oxidative posttranslational modifications. This conceivable accretion of damaged mitochondria in old females might be ascribed to low levels of Parkin, a key mediator of mitophagy. Despite skeletal muscle atrophy and fibrosis, males maintained their testosterone levels throughout aging, as well as their androgen receptor content, and the age-induced mitochondrial remodeling was limited to increased abundance of pyruvate dehydrogenase E1 component subunit beta and electron transfer flavoprotein subunit beta. Herein, for the first time, it was demonstrated that age affects more severely the skeletal muscle mitochondrial proteome of females, reinforcing the necessity of sex-personalized approaches towards sarcopenia management, and the inevitability of the assessment of mitochondrion-related therapeutics.

The impact of out-of-home care on brain development: a brief review of the neuroscientific evidence informing our understanding of children's attachment outcomes.

Researchers interested in the effects of early experiences of caregiving adversity have employed neuroscientific methods to illuminate whether and how such environmental input impacts on brain development, and whether and how such impacts underpin poor socioemotional outcomes in this population. Evidence is compelling in documenting negative effects on the individual's neurodevelopment following exposure to adverse or disadvantaged environments such as institutionalization or maltreatment. Neuroimaging research focused specifically on attachment-relevant processing of socioemotional stimuli and attachment outcomes among children looked-after is scarcer, but largely consistent. This review begins by summarizing the key general brain structural and functional alterations associated with caregiving deprivation. Then, neuroscientific evidence that is more directly relevant for understanding these children's attachment outcomes, both by employing social stimuli and by correlating children's neural markers with their attachment profiles, is reviewed. Brief interpretations of findings are suggested, and key limitations and gaps in the literature identified.

Impact of ozone therapy on mouse liver mitochondrial function and antioxidant system.

Ozone therapy's efficacy might stem from the regulated and mild oxidative stress resulting from ozone's interactions with various biological elements. The present work aimed to characterize the hepatic mitochondrial response to ozone treatment and its relationship with the antioxidant system response. Two groups of mice were used: one control group and another injected intraperitoneally with an O3/O2 mixture (80 ml/kg) for 5 days. Mitochondrial respiration supported by different substrates was significantly inhibited, as well as complexes I and II/III, but not complex IV. The analysis of the electron transport chain complex activity showed significant inhibitions in complexes I and II/III but not in complex IV. These inhibitions can prevent mitochondrial reactive oxygen species (ROS) production. Additionally, there was a decline in glutathione content, unaccompanied by a rise in its oxidized form. The ozone-treated groups showed a significant increase in the activity of superoxide dismutase and glutathione peroxidase, while catalase and glutathione reductase experienced no significant alterations. Adenine nucleotides increased in the ozone group, but only the increase in adenosine diphosphate is significant, so the cell's energy charge is unaffected. This study shows that mitochondria may play a crucial role in ozone treatment. However, it also highlights the need for further studies to understand the molecular mechanism.

The ß-catenin C terminus links Wnt and sphingosine-1-phosphate signaling pathways to promote vascular remodeling and atherosclerosis.

Canonical Wnt and sphingosine-1-phosphate (S1P) signaling pathways are highly conserved systems that contribute to normal vertebrate development, with key consequences for immune, nervous, and cardiovascular system function; despite these functional overlaps, little is known about Wnt/ß-catenin-S1P cross-talk. In the vascular system, both Wnt/ß-catenin and S1P signals affect vessel maturation, stability, and barrier function, but information regarding their potential coordination is scant. We report an instance of functional interaction between the two pathways, including evidence that S1P receptor 1 (S1PR1) is a transcriptional target of ß-catenin. By studying vascular smooth muscle cells and arterial injury response, we find a specific requirement for the ß-catenin carboxyl terminus, which acts to induce S1PR1, and show that this interaction is essential for vascular remodeling. We also report that pharmacological inhibition of the ß-catenin carboxyl terminus reduces S1PR1 expression, neointima formation, and atherosclerosis. These findings provide mechanistic understanding of how Wnt/ß-catenin and S1P systems collaborate during vascular remodeling and inform strategies for therapeutic manipulation.

PolyGR and polyPR knock-in mice reveal a conserved neuroprotective extracellular matrix signature in C9orf72 ALS/FTD neurons.

Dipeptide repeat proteins are a major pathogenic feature of C9orf72 amyotrophic lateral sclerosis (C9ALS)/frontotemporal dementia (FTD) pathology, but their physiological impact has yet to be fully determined. Here we generated C9orf72 dipeptide repeat knock-in mouse models characterized by expression of 400 codon-optimized polyGR or polyPR repeats, and heterozygous C9orf72 reduction. (GR)400 and (PR)400 knock-in mice recapitulate key features of C9ALS/FTD, including cortical neuronal hyperexcitability, age-dependent spinal motor neuron loss and progressive motor dysfunction. Quantitative proteomics revealed an increase in extracellular matrix (ECM) proteins in (GR)400 and (PR)400 spinal cord, with the collagen COL6A1 the most increased protein. TGF-ß1 was one of the top predicted regulators of this ECM signature and polyGR expression in human induced pluripotent stem cell neurons was sufficient to induce TGF-ß1 followed by COL6A1. Knockdown of TGF-ß1 or COL6A1 orthologues in polyGR model Drosophila exacerbated neurodegeneration, while expression of TGF-ß1 or COL6A1 in induced pluripotent stem cell-derived motor neurons of patients with C9ALS/FTD protected against glutamate-induced cell death. Altogether, our findings reveal a neuroprotective and conserved ECM signature in C9ALS/FTD.

Investigation of occupational risk factors for the development of non-Hodgkin's lymphoma in adults: A hospital-based case-control study.

Non-Hodgkin's Lymphoma (NHL) is a malignancy of the lymphoid lineage of the hematopoietic system has worldwide, especially in developed countries. Better diagnostic and recording techniques, longer life expectancy, and greater exposure to risk factors are hypotheses for this growing incidence curve. Occupational exposures to chemical, biological, and physical agents have also been associated with NHL development, but the results are still controversial. We have investigated the occupational and lifestyle case-control study design with 214 adult patients and 452 population controls. Socio-demographic, clinical, and occupational exposure data were obtained through individual interviews with a standardized questionnaire. Clinical, laboratory, and histopathological data were obtained through medical records. Risk of NHL (any subtype), B-cell lymphoma, DLBCL, Follicular lymphoma and T-cell lymphoma was elevated among the those who had ever been exposed to any solvents, hydrocarbon solvents, pesticides, meat and meat products, and sunlight and tended to increase by years of exposure. A significant upward trend with years of exposure was detected for any solvents and hydrocarbon solvents (NHL (any subtype) p-value for trend<0.001), B-cell lymphoma (p-value for trend<0.001), and T-cell lymphoma (p-value for trend<0.023), pesticides (NHL (any subtype), p for trend<0.001) and T-cell lymphoma (p for trend<0.002), meat and meat products (NHL (any subtype) (p for trend<0.001) and DLBCL (p for trend<0.001), and sunlight (B-cell lymphoma (p for trend<0.001). The results of this study agree line with other international studies, can be extrapolated to other countries that have the same socio-demographic and occupational characteristics as Brazil and support strategies for surveillance and control of work-related cancer.

Postintervention Immunological and Entomological Survey of Lymphatic Filariasis in the City of Olinda, Brazil, 2015-2016.

Lymphatic filariasis (LF) is a leading cause of disability due to infectious disease worldwide. The Recife Metropolitan Region (RMR) is the only remaining focus of LF in Brazil, where the parasite Wuchereria bancrofti is transmitted solely by the mosquito Culex quinquefasciatus. This study reports the results of transmission assessment surveys and molecular xenomonitoring in the city of Olinda, RMR, after nearly 15 years (2015-2016) of interventions for LF elimination. Participants were screened for W. bancrofti antigen via immunochromatographic card tests (ICT) in: 1) door-to-door surveys conducted for all children aged 5-7 years from 4 out of 17 intervention areas treated with at least five annual doses of mass drug administration (MDA), and 2) a two-stage cluster sampling survey of residents aged 5 years and older in non-MDA areas. Mosquitoes were collected via handheld aspirators in four MDA areas, differentiated by species, sex, and physiological status, pooled into groups of up to 10 blood-fed, semigravid, and gravid mosquitoes, and screened for W. bancrofti infection by real-time quantitative polymerase chain reaction (RT-qPCR). All 1,170 children from MDA areas and the entire population sample of 990 residents in non-MDA areas were ICT negative. In MDA areas, a total of 3,152 female Cx. quinquefasciatus mosquitoes in 277 households (range, 0-296 mosquitoes per house) were collected via aspiration. RT-qPCR of 233 pools of mosquitos were negative for W. bancrofti RNA; an independent reference laboratory confirmed these results. These results provide evidence that LF transmission has been halted in this setting.

Osseointegration of implant surfaces in metabolic syndrome and type-2 diabetes mellitus.

This in vivo study evaluated the bone healing response around endosteal implants with varying surface topography/chemistry in a preclinical, large transitional model induced with metabolic syndrome (MS) and type-2 diabetes mellitus (T2DM). Fifteen Göttingen minipigs were randomly distributed into two groups: (i) control (normal diet, n = 5) and (ii) O/MS (cafeteria diet for obesity induction, n = 10). Following obesity induction, five minipigs from the obese/metabolic syndrome (O/MS) group were further allocated, randomly, into the third experimental group: (iii) T2DM (cafeteria diet + streptozotocin). Implants with different surface topography/chemistry: (i) dual acid-etched (DAE) and (ii) nano-hydroxyapatite coating over the DAE surface (NANO), were placed into the right ilium of the subjects and allowed to heal for 4 weeks. Histomorphometric evaluation of bone-to-implant contact (%BIC) and bone area fraction occupancy (%BAFO) within implant threads were performed using histomicrographs. Implants with NANO surface presented significantly higher %BIC (~26%) and %BAFO (~35%) relative to implants with DAE surface (%BIC = ~14% and %BAFO = ~28%, p < .025). Data as a function of systemic condition presented significantly higher %BIC (~28%) and %BAFO (~42%) in the control group compared with the metabolically compromised groups (O/MS: %BIC = 14.35% and %BAFO = 26.24%, p < .021; T2DM: %BIC = 17.91% and %BAFO = 26.12%, p < .021) with no significant difference between O/MS and T2DM (p > .05). Statistical evaluation considering both factors demonstrated significantly higher %BIC and %BAFO for the NANO surface relative to DAE implant, independent of systemic condition (p < .05). The gain increase of %BIC and %BAFO for the NANO compared with DAE was more pronounced in O/MS and T2DM subjects. Osseointegration parameters were significantly reduced in metabolically compromised subjects compared with healthy subjects. Nanostructured hydroxyapatite-coated surfaces improved osseointegration relative to DAE, regardless of systemic condition.

Inhibitors of gastric acid secretion increase oxidative stress and matrix metalloproteinase-2 activity leading to vascular remodeling.

The use of inhibitors of gastric acid secretion (IGAS), especially proton pump inhibitors (PPI), has been associated with increased cardiovascular risk. While the mechanisms involved are not known, there is evidence supporting increased oxidative stress, a major activator of matrix metalloproteinases (MMP), as an important player in such effect. However, there is no study showing whether other IGAS such as histamine H2-receptor blockers (H2RB) cause similar effects. This study aimed at examining whether treatment with the H2RB ranitidine promotes oxidative stress resulting in vascular MMP activation and corresponding functional and structural alterations in the vasculature, as compared with those found with the PPI omeprazole. Male Wistar rats were treated (4 weeks) with vehicle (2% tween 20), omeprazole (10 mg/Kg/day; i.p.) or ranitidine (100 mg/Kg/day; gavage). Then the aorta was collected to perform functional, biochemical, and morphometric analysis. Both ranitidine and omeprazole increased gastric pH and oxidative stress assessed in situ with the fluorescent dye dihydroethidium (DHE) and with lucigenin chemiluminescence assay. Both IGAS augmented vascular activated MMP-2. These findings were associated with aortic remodeling (increased media/lumen ratio and number of cells/µm2). Both IGAS also impaired the endothelium-dependent relaxation induced by acetylcholine (isolated aortic ring preparation). This study provides evidence that the H2RB ranitidine induces vascular dysfunction, redox alterations, and remodeling similar to those found with the PPI omeprazole. These findings strongly suggest that IGAS increase oxidative stress and matrix metalloproteinase-2 activity leading to vascular remodeling, which helps to explain the increased cardiovascular risk associated with the use of those drugs.

The first full study of heavy metal(loid)s in western-European hedgehogs (Erinaceus europaeus) from Portugal.

The western-European hedgehog (Erinaceus europaeus) is an insectivore with a wide distribution in Portugal and a potential tool for biomonitoring relevant One Health hazards, including heavy metal(loid)s' pollution. The aim of this study was to positively contribute to the current knowledge about the metal(loid) pollution in Portugal. Forty-six hedgehogs (from rescue centres; with known provenance) were necropsied. Sex, age category and weight were determined. Spines, liver and kidney were collected, and metalloid concentrations were determined by inductively coupled plasma mass spectrophotometry (ICP-MS). In general, results did not present alarming metal(loid) concentrations, with the exception of cadmium (Cd) (in the kidneys) and copper (Cu). Hedgehogs from Viana do Castelo and Viseu showed elevated concentrations of arsenic (As) and Castelo Branco presented concerning values of cadmium (Cd). Adult and heavier hedgehogs tended to present higher levels of metal(loid)s. Sex does not seem to significantly affect the metal(loid)s' concentrations. Further analysis would be needed to prioritize areas with detail and allow the application of the necessary mitigation strategies.

Guidelines on Developmental Toxicity Tests: Brief Insights.

Developmental toxicology is a constantly evolving research field which needs to attend to a complex underlying regulatory network. In order to ensure human health and environmental safety, new substances have to be tested for toxic effects on reproduction and development, before being commercialized. Traditional in vivo mammalian models represent the intricacy of human development and provide more adequately an assessment of the interaction of chemical compounds with the reproductive system. However, in the last years, the directives are to reduce the use of vertebrate animals, promoting their use only as a last resort. Consequently, the interest on the development and validation of alternative tests, able to cover the various aspects of the reproductive cycle, has significantly increased. Reproductive toxicity is probably the most difficult endpoint to be replaced by alternative assays, since it should provide information on mechanism interactions essential for female and male fertility and also knowledge on the animal development during the first phases of its life cycle. This complexity explains the slow progress in implementing alternative models for reproductive toxicity safety assays. Alternative test models may be based on in vitro systems and nonmammalian animal models. Many biological processes have been successfully addressed using in vitro models, opening the possibility to study the interference of teratogenic compounds. Their validation and implementation have lagged behind, in part because of difficulties in establishing their predictability. Nevertheless, the advance toward the process of validation is crucial to replace and reduce the use of living animals. Based on the present state of the art, it is not probable that such testing strategies will completely replace the need to assess reproductive toxicity in vivo in the near future, but they will contribute to reduce animal tests and will provide important information. In this chapter, the approved guidelines for standard methods and alternative methods, according to their regulatory and scientific status, are enumerated and briefly described.

Development Features on the Selection of Animal Models for Teratogenic Testing.

Today, the use of animal models from different species continues to represent a fundamental step in teratogenic testing, despite the increase in alternative solutions that provide an important screening to the enormous quantity of new substances that aim to enter the market every year. The maintenance of these models is due to the sharing of similar development processes with humans, and in this way they represent an important contribution to the safety in the use of the compounds tested. Furthermore, the application of advances in embryology to teratology, although hampered by the complexity of reproductive processes, continues to prove the importance of sensitivity during embryonic and fetal development to detect potential toxicity, inducing mortality/abortion and malformations.In this chapter, essential periods of development in different models are outlined, highlighting the similarities and differences between species, the advantages and disadvantages of each group, and specific sensitivities for teratogenic testing. Models can be divided into invertebrate species such as earthworms of the species Eisenia fetida/Eisenia andrei, Caenorhabditis elegans, and Drosophila melanogaster, allowing for rapid results and minor ethical concerns. Vertebrate nonmammalian species Xenopus laevis and Danio rerio are important models to assess teratogenic potential later in development with fewer ethical requirements. Finally, the mammalian species Mus musculus, Rattus norvegicus, and Oryctolagus cuniculus, phylogenetically closer to humans, are essential for the assessment of complex specialized processes, occurring later in development.Regulations for the development of toxicology tests require the use of mammalian species. Although ethical concerns and costs limit their use in large-scale screening. On the other hand, invertebrate and vertebrate nonmammalian species are increasing as alternative animal models, as these organisms combine low cost, less ethical requirements, and culture conditions compatible with large-scale screening. Their main advantage is to allow high-throughput screening in a whole-animal context, in contrast to the in vitro techniques, not dependent on the prior identification of a target. Better knowledge of the development pathways of animal models will allow to maximize human translation and reduce the number of animals used, leading to a selection of compounds with an improved safety profile and reduced time to market for new drugs.

Magnesium and Vascular Calcification in Chronic Kidney Disease: Current Insights.

Magnesium (Mg) plays crucial roles in multiple essential biological processes. As the kidneys are the primary organ responsible for maintaining the blood concentration of Mg, people with chronic kidney disease (CKD) may develop disturbances in Mg. While both hyper- and hypomagnesemia may lead to adverse effects, the consequences associated with hypomagnesemia are often more severe and lasting. Importantly, observational studies have shown that CKD patients with hypomagnesemia have greater vascular calcification. Vascular calcification is accelerated and contributes to a high mortality rate in the CKD population. Both in vitro and animal studies have demonstrated that Mg protects against vascular calcification via several potential mechanisms, such as inhibiting the formation of both hydroxyapatite and pathogenic calciprotein particles as well as limiting osteogenic differentiation, a process in which vascular smooth muscle cells in the media layer of the arteries transform into bone-like cells. These preclinical findings have led to several important clinical trials that have investigated the effects of Mg supplementation on vascular calcification in people with CKD. Interestingly, two major clinical studies produced contradictory findings, resulting in a state of equipoise. This narrative review provides an overview of our current knowledge in the renal handling of Mg in health and CKD and the underlying mechanisms by which Mg may protect against vascular calcification. Lastly, we evaluate the strength of evidence from clinical studies on the efficacy of Mg supplementation and discuss future research directions.

Lifelong exercise training promotes the remodelling of the immune system and prostate signalome in a rat model of prostate carcinogenesis.

This work aimed to understand how lifelong exercise training promotes the remodelling of the immune system and prostate signalome in a rat model of PCa. Fifty-five male Wistar rats were divided into four groups: control sedentary, control exercised, induced PCa sedentary and induced PCa exercised. Exercised animals were trained in a treadmill for 53 weeks. Pca induction consisted on the sequential administration of flutamide, N-methyl-N-nitrosourea and testosterone propionate implants. Serum concentrations of C-reactive protein (CRP) and tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) were not different among groups. Peripheral levels of γδ T cells were higher in Pca exercised group than in the PCa sedentary group (p < 0.05). Exercise training also induced Oestrogen Receptor (ESR1) upregulation and Mitogen-activated Protein Kinase 13 (MAPK13) downregulation, changed the content of the phosphorylated (at Ser-104) form of this receptor (coded by the gene ESR1) and seemed to increase Erα phosphorylation and activity in exercised PCa rats when compared with sedentary PCa rats. Our data highlight the exercise-induced remodelling of peripheral lymphocyte subpopulations and lymphocyte infiltration in prostate tissue. Moreover, exercise training promotes the remodelling prostate signalome in this rat model of prostate carcinogenesis.

Evaluation of the anti-inflammatory effect of 1,4-dihydropyridine derivatives.

INTRODUCTION: Inflammation is a physiological event that protects the organism against different factors that lead to loss of tissue homeostasis. Dihydropyridine (DHP) derivatives are heterocyclic compounds known for their different biological activities, including anti-inflammatory activities. OBJECTIVE: To evaluate the anti-inflammatory activity of 1,4-dihydropyridine (1,4-DHP) derivatives using anti-inflammatory models in vitro, in RAW264.7 cells induced by lipopolysaccharide (LPS) and in vivo using the acute lung injury (ALI) model in mice. RESULTS: Fifteen compounds derived from 1,4-DHP were tested in RAW264.7 cells for their cytotoxic effect and cell viability. Thereafter, only the six compounds that showed the highest cell viability were tested for the production or inhibition of the pro-inflammatory cytokine interleukin 6 (IL-6). The best compound (compound 4) was tested for its anti-inflammatory effects in vitro and in vivo, showing inhibition of nitric oxide (NO), pro-inflammatory cytokines, increased phagocytic activity, and an increase in IL-10 in vitro. In in vivo tests, compound 4 also reduces the levels of NO, myeloperoxidase (MPO) activity, leukocyte migration, and exudation, as well as reducing the levels of tumor necrosis factor-alpha (TNF-α) and IL-6 and preventing the loss in the lung architecture. CONCLUSION: This compound showed important anti-inflammatory activity, with a significant ability to reduce the production of pro-inflammatory mediators and increase the phagocytic activity of macrophages and anti-inflammatory mediator secretion (IL-10). These findings led us to hypothesize that this compound can repolarize the macrophage response to an anti-inflammatory profile (M2). Moreover, it was also able to maintain its anti-inflammatory activity in vivo experiments.

Current views on in vivo models for breast cancer research and related drug development.

INTRODUCTION: Animal models play a crucial role in breast cancer research, in particular mice and rats, who develop mammary tumors that closely resemble their human counterparts. These models allow the study of mechanisms behind breast carcinogenesis, as well as the efficacy and safety of new, and potentially more effective and advantageous therapeutic approaches. Understanding the advantages and disadvantages of each model is crucial to select the most appropriate one for the research purpose. AREA COVERED: This review provides a concise overview of the animal models available for breast cancer research, discussing the advantages and disadvantages of each one for searching new and more effective approaches to treatments for this type of cancer. EXPERT OPINION: Rodent models provide valuable information on the genetic alterations of the disease, the tumor microenvironment, and allow the evaluation of the efficacy of chemotherapeutic agents. However, in vivo models have limitations, and one of them is the fact that they do not fully mimic human diseases. Choosing the most suitable model for the study purpose is crucial for the development of new therapeutic agents that provide better care for breast cancer patients.

Adherence to Exercise Training and Physical Function in Older Adults Diagnosed with Knee Osteoarthritis.

Background: Knee osteoarthritis (KOA) provokes pain, muscle weakness, and consequent impairment in activities of daily living. On the other hand, adherence to exercise training (ET) is associated with the attenuation of the impairments. The aims of the present study were to a) investigate adherence to ET in older adults with KOA diagnosed attending public service; and b) to analyze the physical function of the older adults with KOA who did not adhere to the ET in public service. Methods: The adherence to ET programs was analyzed retrospectively from each patient's date of KOA diagnosis. After assessing the adherence to ET, the physical function of these older adults diagnosed with KOA (n=19) was analyzed and compared with another group composed of asymptomatic sedentary older adults without evidence of KOA (ASKOA) (n=17). Results: Although all older adults with KOA received guidelines to practice ET, only 58% were able to start a program. Additionally, 100% of the sample could not perform ET uninterruptedly. According to the findings, close to 80% of older adults had difficulties scheduling ET sessions in public places. Subjects with KOA (12.1±3.1; IC95%:10.6-13.6) had worse lower limb functional capacity than ASKOA (8.1±1.0; IC95%:7.6-8.6; p<.001; δ=4.0 sec; d=1.7). Likewise, they had a lower dynamic balance than KOA (12.4±2.7; IC95%:11.1-13.7 vs. 8.0±1.1; IC95%:7.4-8.6; p<.001; δ=4.4 sec; d=2.1). Conclusions: The investigated sample has a lack of ET adherence by difficulties in scheduling ET sessions in public places. In addition, it demonstrated impairment in physical function in older adults with KOA.

Heavy metals and metalloids in wild boars (Sus Scrofa) - a silent but serious public health hazard.

Wild boars (Sus scrofa) are part of the hunting economy and are highly consumed in the Iberian Peninsula, including in the Castile and Leon regions. As zoonotic diseases, chemical pollutants in wild boars' internal tissues should be interpreted as evidence of environmental contamination and a matter of concern for animal, human and ecosystem health; in other words, a One Health concern. Twenty-eight wild boars' livers and kidneys (n = 28) from Castile and Leon were submitted to metal(loid) determination (As, Cd, Co, Cr, Cu, Ni, Pb, and Zn) with inductively coupled plasma mass spectrophotometry (ICP-MS) and histopathological exam. Cd levels, especially in the kidneys (7.063 ± 7.271 mg/kg dw), were the most concerning results, considering the calculated maximum values for consumption (EC No. 915/2023) (2.491 mg/kg dw or 1.0 mg/kg ww). Wild boars with hydropic changes in the liver presented higher concentrations of Ni. Thus, the metal(loid) contamination of wild boar carcasses seems to be a "no trace" but very relevant problem that should raise awareness of a more accurate monitoring program and other strategies to avoid public health consequences.

Klotho in Cancer: Potential Diagnostic and Prognostic Applications.

Klotho proteins, αKlotho, ßKlotho, and γKlotho, exert tumor-suppressive activities via the fibroblast growth factor receptors and multiple cell-signaling pathways. There is a growing interest in Klotho proteins as potential diagnostic and prognostic biomarkers for multiple diseases. However, recent advances regarding their roles and potential applications in cancer remain disperse and require an integrated analysis. The present review analyzed research articles published between 2012 and 2022 in the Cochrane and Scopus scientific databases to study the role of Klotho in cancer and their potential as tools for diagnosing specific cancer types, predicting tumor aggressiveness and prognosis. Twenty-six articles were selected, dealing with acute myeloid leukemia and with bladder, breast, colorectal, esophageal, gastric, hepatocellular, ovarian, pancreatic, prostatic, pulmonary, renal, and thyroid cancers. αKlotho was consistently associated with improved prognosis and may be useful in estimating patient survival. A single study reported the use of soluble αKlotho levels in blood serum as a tool to aid the diagnosis of esophageal cancer. γKlotho was associated with increased aggressiveness of bladder, breast, and prostate cancer, and ßKlotho showed mixed results. Further clinical development of Klotho-based assays will require careful identification of specific tumor subtypes where Klotho proteins may be most valuable as diagnostic or prognostic tools.